Circadian rhythms are endogenous oscillations coordinating the physiological and behavioral activities with the daily light-dark cycle and are controlled by molecular mechanisms. Nicotinamide adenine dinucleotide (NAD+), a critical cofactor in redox processes and a substrate for many enzymes, is an important metabolite in circadian rhythms. NAD+ levels show strong circadian oscillations, which are caused by the rhythmic production of biosynthetic enzymes such as nicotinamide phosphoribosyl transferase. In contrast, the circadian clock system regulates the expression of NAD+ biosynthetic enzymes, resulting in a bidirectional regulatory loop. Sirtuins, a class of NAD+-dependent protein deacetylases, regulate the circadian clock by interacting with the core clock components and transcriptional regulators. Sirtuin (SIRT) 1 deacetylates and modulates the activity of key circadian transcription factors such as brain and muscle arnt-like 1 and period circadian regulator 2, while SIRT6 regulates the expression of circadian-controlled metabolic genes. This review explored the complex relationships among NAD+, sirtuins, and the circadian clock machinery, emphasizing their roles in sustaining metabolic homeostasis and coordinating cellular processes with daily environmental cycles. Moreover, circadian disruptions are strongly associated with aging, which results in the dysregulation of NAD+ homeostasis and sirtuin activity and contributes to the development of various age-related pathologies. Strategies to restore NAD+ levels or modify the sirtuin activity have emerged as promising treatment options for circadian rhythm disturbances and age-related disorders. This review also aimed to cover new horizons in this subject, such as the development of NAD+ boosters and sirtuin modulators, chrono-pharmacological methods, and the study of epigenetic mechanisms underlying sirtuin-mediated circadian regulation.

Circadian rhythms are endogenous oscillations coordinating the physiological and behavioral activities with the daily light-dark cycle and are controlled by molecular mechanisms. Nicotinamide adenine dinucleotide (NAD+), a critical cofactor in redox processes and a substrate for many enzymes, is an important metabolite in circadian rhythms. NAD+ levels show strong circadian oscillations, which are caused by the rhythmic production of biosynthetic enzymes such as nicotinamide phosphoribosyl transferase. In contrast, the circadian clock system regulates the expression of NAD+ biosynthetic enzymes, resulting in a bidirectional regulatory loop. Sirtuins, a class of NAD+-dependent protein deacetylases, regulate the circadian clock by interacting with the core clock components and transcriptional regulators. Sirtuin (SIRT) 1 deacetylates and modulates the activity of key circadian transcription factors such as brain and muscle arnt-like 1 and period circadian regulator 2, while SIRT6 regulates the expression of circadian-controlled metabolic genes. This review explored the complex relationships among NAD+, sirtuins, and the circadian clock machinery, emphasizing their roles in sustaining metabolic homeostasis and coordinating cellular processes with daily environmental cycles. Moreover, circadian disruptions are strongly associated with aging, which results in the dysregulation of NAD+ homeostasis and sirtuin activity and contributes to the development of various age-related pathologies. Strategies to restore NAD+ levels or modify the sirtuin activity have emerged as promising treatment options for circadian rhythm disturbances and age-related disorders. This review also aimed to cover new horizons in this subject, such as the development of NAD+ boosters and sirtuin modulators, chrono-pharmacological methods, and the study of epigenetic mechanisms underlying sirtuin-mediated circadian regulation.

Circadian rhythms are endogenous oscillations coordinating the physiological and behavioral activities with the daily light-dark cycle and are controlled by molecular mechanisms. Nicotinamide adenine dinucleotide (NAD+), a critical cofactor in redox processes and a substrate for many enzymes, is an important metabolite in circadian rhythms. NAD+ levels show strong circadian oscillations, which are caused by the rhythmic production of biosynthetic enzymes such as nicotinamide phosphoribosyl transferase. In contrast, the circadian clock system regulates the expression of NAD+ biosynthetic enzymes, resulting in a bidirectional regulatory loop. Sirtuins, a class of NAD+-dependent protein deacetylases, regulate the circadian clock by interacting with the core clock components and transcriptional regulators. Sirtuin (SIRT) 1 deacetylates and modulates the activity of key circadian transcription factors such as brain and muscle arnt-like 1 and period circadian regulator 2, while SIRT6 regulates the expression of circadian-controlled metabolic genes. This review explored the complex relationships among NAD+, sirtuins, and the circadian clock machinery, emphasizing their roles in sustaining metabolic homeostasis and coordinating cellular processes with daily environmental cycles. Moreover, circadian disruptions are strongly associated with aging, which results in the dysregulation of NAD+ homeostasis and sirtuin activity and contributes to the development of various age-related pathologies. Strategies to restore NAD+ levels or modify the sirtuin activity have emerged as promising treatment options for circadian rhythm disturbances and age-related disorders. This review also aimed to cover new horizons in this subject, such as the development of NAD+ boosters and sirtuin modulators, chrono-pharmacological methods, and the study of epigenetic mechanisms underlying sirtuin-mediated circadian regulation.

BACKGROUND: We are presenting our experience in the use of locking compression plate (LCP) after juxta-articular oncological resections in addition to its use in pathologic fracture. METHODS: A retrospective audit of skeletal reconstruction using LCP in 25 cases of long bone tumors was performed from 2008 to 2010. Reconstruction following limb salvage surgery was done in 17 patients and internal fixation of pathological fracture was done in 8 patients. All patients were available for > 12 months of follow-up, and thus assessed for union at the resected ends. RESULTS: There were 8 males and 17 females in the study. The average age at the time of surgery was 30 years (range, 9 to 66 years). The minimum follow-up was 12 months (range, 12 to 32 months). All patients except three went on to heal successfully. Complications occurred in those three patients: wound infection in one, nonunion in another, and periprosthetic fracture in the other patient. In the remaining patients, union was achieved at an average of 6.5 months after reconstruction in curative resection and 4.75 months after fixation of pathological fractures. CONCLUSIONS: Joint sparing limb salvage surgery was made successfully possible after sekeletal reconstruction with LCP. Its use was also quite effective in pathological fractures with poor bone quality. Use of locking plates for musculoskeletal oncological reconstruction resulted in a good and predictable rate of union.
Adolescent ; Adult ; Aged ; Bone Neoplasms/complications/radiography/*surgery ; Bone Plates ; Child ; Female ; Fractures, Spontaneous/etiology/radiography/*surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Retrospective Studies ; Young Adult